Hepatocellular carcinoma of viral and non-viral etiologies has similar survival outcomes following curative intent surgical resection: a retrospective cohort study

Introduction: Despite the broad impression that non- Hepatitis B virus (HBV)-non-Hepatitis C virus (HCV) (NBNC) hepatocellular carcinoma (HCC) has poorer tumor characteristics, there is conflicting literature on whether this translates to poorer survival outcomes post-resection compared to their viral counterparts. We compared the relative impact of chronic viral status and intrinsic liver function on outcomes between NBNC and viral-HCC patients post-resection after matching for tumor stage. Methods: This retrospective cohort study examines consecutive patients undergoing curative-intent resection for HCC at our institution between January 2000 and June 2016. Extrahepatic disease, tumor rupture, palliative-intent resection, and concurrent second primaries were excluded. Intrinsic liver function was assessed by albumin-bilirubin (ALBI) grade and Child-Pugh class. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS). To address baseline imbalances, 1:1 nearest-neighbor propensity score matching (PSM) was performed based on Barcelona Clinic for Liver Cancer stage. A multivariate Cox model identified independent prognostic factors. Results: 690 of 1043 patients met all inclusion and exclusion criteria (HBV: 452, HCV: 56, NBNC: 182), and PSM yielded 364 (Viral: 182, NBNC: 182) with excellent balance. The median OS for viral was 52.2 months, which was comparable to 59.0 months in the NBNC group ( P = 0.5). Five-year OS and RFS differed by ALBI grade (Grade 1: 60.5% and 44.9% vs. Grade 2: 41.0% and 28.0%, both P < 0.001) but not by viral status within the ALBI strata. On multivariate analysis, higher ALBI grade ( P = 0.01), presence of microvascular invasion ( P < 0.001), and elevated alpha-fetal protein level > 400 ng/mL ( P = 0.04) were independent predictors of RFS. Viral status was not associated with OS ( P = 0.90) or RFS ( P = 0.70). Conclusion: After matching for tumor stage, viral status does not independently determine post-resection prognosis. Intrinsic hepatic reserve, measured by ALBI grade, is a better discriminator of outcome and should guide risk stratification, selection for transplantation versus resection, and tailoring of adjuvant therapies.